Variant rs2305035 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_170662.5(CBLB):c.1272C>T(p.Asp424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,612,752 control chromosomes in the GnomAD database, including 39,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3630 hom., cov: 31)

Exomes 𝑓: 0.22 ( 36168 hom. )

Consequence

CBLB
NM_170662.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.160

Variant links:

Genes affected

CBLB (HGNC:1542): (Cbl proto-oncogene B) This gene encodes an E3 ubiquitin-protein ligase which promotes proteosome-mediated protein degradation by transferring ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate. The encoded protein is involved in the regulation of immune response by limiting T-cell receptor, B-cell receptor, and high affinity immunoglobulin epsilon receptor activation. Studies in mouse suggest that this gene is involved in antifungal host defense and that its inhibition leads to increased fungal killing. Manipulation of this gene may be beneficial in implementing immunotherapies for a variety of conditions, including cancer, autoimmune diseases, allergies, and infections. [provided by RefSeq, Sep 2017]

CBLB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 3-105720182-G-A is Benign according to our data. Variant chr3-105720182-G-A is described in ClinVar as [Benign]. Clinvar id is 3055764.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLB	NM_170662.5 linkuse as main transcript	c.1272C>T	p.Asp424=	synonymous_variant	10/19	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030.8 linkuse as main transcript	c.1272C>T	p.Asp424=	synonymous_variant	10/19	1	NM_170662.5	ENSP00000377598	P1	Q13191-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32599

AN:

151802

Hom.:

3625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.225

AC:

56304

AN:

250508

Hom.:

6728

AF XY:

0.218

AC XY:

29535

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.219

AC:

320188

AN:

1460832

Hom.:

36168

Cov.:

AF XY:

0.217

AC XY:

157441

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.215

AC:

32623

AN:

151920

Hom.:

3630

Cov.:

AF XY:

0.217

AC XY:

16136

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.213

Hom.:

5890

Bravo

AF:

0.215

Asia WGS

AF:

0.169

AC:

588

AN:

3478

EpiCase

AF:

0.215

EpiControl

AF:

0.205

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CBLB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.5

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over